RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling
| العنوان: | RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling |
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| المؤلفون: | Yue Zhang, Xiaoying Shi, Peter Finan, Feng Cong, Craig Mickanin, Olga Charlat, Marc Hild, Yan Feng, Gregory A. Michaud, Shanming Liu, Andreas Bauer, Jeffery A. Porter, Markus Schirle, Shih-Min A. Huang, Vic E. Myer |
| المصدر: | Nature Cell Biology. 13:623-629 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Poly Adenosine Diphosphate Ribose, Ubiquitin-Protein Ligases, Molecular Sequence Data, Protein degradation, Axin Protein, Ubiquitin, Animals, Humans, Amino Acid Sequence, Tissue homeostasis, Adaptor Proteins, Signal Transducing, Sequence Homology, Amino Acid, biology, Hydrolysis, Wnt signaling pathway, Signal transducing adaptor protein, Cell Biology, Hedgehog signaling pathway, Cell biology, Ubiquitin ligase, Repressor Proteins, Wnt Proteins, Biochemistry, biology.protein, Signal Transduction |
| الوصف: | The Wnt/β-catenin signalling pathway plays essential roles in embryonic development and adult tissue homeostasis, and deregulation of this pathway has been linked to cancer. Axin is a concentration-limiting component of the β-catenin destruction complex, and its stability is regulated by tankyrase. However, the molecular mechanism by which tankyrase-dependent poly(ADP-ribosyl)ation (PARsylation) is coupled to ubiquitylation and degradation of axin remains undefined. Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. Thus, identification of RNF146 as a PARsylation-directed E3 ligase establishes a molecular paradigm that links tankyrase-dependent PARsylation to ubiquitylation. RNF146-dependent protein degradation may emerge as a major mechanism by which tankyrase exerts its function. |
| تدمد: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb2222 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eae1f21f11d41b259941e917c656dd30 https://doi.org/10.1038/ncb2222 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....eae1f21f11d41b259941e917c656dd30 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764679 14657392 |
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| DOI: | 10.1038/ncb2222 |